Fetal programming of pulmonary vascular dysfunction in mice: role of epigenetic mechanisms.

Insults during the fetal period predispose the offspring to systemic cardiovascular disease, but little is known about the pulmonary circulation and the underlying mechanisms. Maternal undernutrition during pregnancy may represent a model to investigate underlying mechanisms, because it is associated with systemic vascular dysfunction in the offspring in animals and humans. In rats, restrictive diet during pregnancy (RDP) increases oxidative stress in the placenta. Oxygen species are known to induce epigenetic alterations and may cross the placental barrier. We hypothesized that RDP in mice induces pulmonary vascular dysfunction in the offspring that is related to an epigenetic mechanism. To test this hypothesis, we assessed pulmonary vascular function and lung DNA methylation in offspring of RDP and in control mice at the end of a 2-wk exposure to hypoxia. We found that endothelium-dependent pulmonary artery vasodilation in vitro was impaired and hypoxia-induced pulmonary hypertension and right ventricular hypertrophy in vivo were exaggerated in offspring of RDP. This pulmonary vascular dysfunction was associated with altered lung DNA methylation. Administration of the histone deacetylase inhibitors butyrate and trichostatin A to offspring of RDP normalized pulmonary DNA methylation and vascular function. Finally, administration of the nitroxide Tempol to the mother during RDP prevented vascular dysfunction and dysmethylation in the offspring. These findings demonstrate that in mice undernutrition during gestation induces pulmonary vascular dysfunction in the offspring by an epigenetic mechanism. A similar mechanism may be involved in the fetal programming of vascular dysfunction in humans.

Evaluation and comparison of current fetal ultrasound image segmentation methods for biometric measurements: a grand challenge.

This paper presents the evaluation results of the methods submitted to Challenge US: Biometric Measurements from Fetal Ultrasound Images, a segmentation challenge held at the IEEE International Symposium on Biomedical Imaging 2012. The challenge was set to compare and evaluate current fetal ultrasound image segmentation methods. It consisted of automatically segmenting fetal anatomical structures to measure standard obstetric biometric parameters, from 2D fetal ultrasound images taken on fetuses at different gestational ages (21 weeks, 28 weeks, and 33 weeks) and with varying image quality to reflect data encountered in real clinical environments. Four independent sub-challenges were proposed, according to the objects of interest measured in clinical practice: abdomen, head, femur, and whole fetus. Five teams participated in the head sub-challenge and two teams in the femur sub-challenge, including one team who tackled both. Nobody attempted the abdomen and whole fetus sub-challenges. The challenge goals were two-fold and the participants were asked to submit the segmentation results as well as the measurements derived from the segmented objects. Extensive quantitative (region-based, distance-based, and Bland-Altman measurements) and qualitative evaluation was performed to compare the results from a representative selection of current methods submitted to the challenge. Several experts (three for the head sub-challenge and two for the femur sub-challenge), with different degrees of expertise, manually delineated the objects of interest to define the ground truth used within the evaluation framework. For the head sub-challenge, several groups produced results that could be potentially used in clinical settings, with comparable performance to manual delineations. The femur sub-challenge had inferior performance to the head sub-challenge due to the fact that it is a harder segmentation problem and that the techniques presented relied more on the femur's appearance.

Thymus-independent generation of NK1+ T cells in vitro from fetal liver precursors.

NK1.1+TCR alpha beta+ (NK1+) T cells are an unusual subset of mouse TCR alpha beta+ cells found primarily in adult thymus and liver. In contrast to conventional TCR alpha beta+ cells, NK1+ T cells have a TCR repertoire that is highly skewed to V alpha14 and to Vbeta8, -7, and -2. The developmental origin and ligand specificity of NK1+ T cells are controversial. We show here that NK1+ T cells with a typically biased V alpha and V beta repertoire develop in cytokine-supplemented suspension cultures of fetal liver established from either normal or athymic mice. Furthermore, NK1+ T cell development in fetal liver cultures is abrogated in beta2m-deficient mice (which lack MHC class I and other related molecules) and can be partially inhibited by the presence of anti-CD1 mAbs. Moreover, mixing experiments indicate that recombination-deficient SCID fetal liver cells can reconstitute NK1+ T cell development in beta2m-deficient fetal liver cultures. Collectively, our data demonstrate that NK1+ T cells can develop extrathymically from fetal liver precursors and that a beta2m-associated ligand (putatively CD1) present on nonlymphoid cells is essential for their positive selection and/or expansion.

Moxibustión en la malposición fetal

Introducción: La incidencia de la presentación fetal podálica en España es del 3,8%. La moxibustión es parte integral de la milenaria medicina tradicional china. La técnica consiste en la colocación de un palillo incandescente de Artemisia vulgaris a unos pocos centímetros del punto de acupuntura Zhiyin (punto 67 del meridiano de vejiga, ubicado en la base externa de la uña del quinto dedo del pie). Los objetivos son: 1. Conocer el porcentaje de fetos que han rotado a cefálica mediante la moxibustión en gestantes que presenten una malposición fetal a partir de las 32 semanas de embarazo; 2. Identificar las complicaciones materno-fetales en la aplicación de la técnica. Sujetos: Se estudiaron 18 gestantes de más de 32 semanas de embarazo. Material y métodos: Mediante un estudio descriptivo de intervención, analizamos el porcentaje de fetos que rotaron a presentación cefálica. Resultados: Quince gestantes (83,9%) realizaron el tratamiento adecuadamente y las 3 restantes (16,7%) lo realizaron de manera ocasional y terminaron con una cesárea electiva por nalgas. Conclusiones: Parece razonable concluir que el cumplimiento del tratamiento influye en el tipo de parto (χ2= 12,600; gl= 1; p= 0,000), aunque no modifica el Apgar del recién nacido. Esta técnica se presenta como una alternativa económica, segura, sencilla y práctica para la versión fetal de la presentación podálica.

An efficient total variation algorithm for super-resolution in fetal brain MRI with adaptive regularization.

Although fetal anatomy can be adequately viewed in new multi-slice MR images, many critical limitations remain for quantitative data analysis. To this end, several research groups have recently developed advanced image processing methods, often denoted by super-resolution (SR) techniques, to reconstruct from a set of clinical low-resolution (LR) images, a high-resolution (HR) motion-free volume. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has been quite attracted by Total Variation energies because of their ability in edge preserving but only standard explicit steepest gradient techniques have been applied for optimization. In a preliminary work, it has been shown that novel fast convex optimization techniques could be successfully applied to design an efficient Total Variation optimization algorithm for the super-resolution problem. In this work, two major contributions are presented. Firstly, we will briefly review the Bayesian and Variational dual formulations of current state-of-the-art methods dedicated to fetal MRI reconstruction. Secondly, we present an extensive quantitative evaluation of our SR algorithm previously introduced on both simulated fetal and real clinical data (with both normal and pathological subjects). Specifically, we study the robustness of regularization terms in front of residual registration errors and we also present a novel strategy for automatically select the weight of the regularization as regards the data fidelity term. Our results show that our TV implementation is highly robust in front of motion artifacts and that it offers the best trade-off between speed and accuracy for fetal MRI recovery as in comparison with state-of-the art methods.

Dopplerfluxometria no estudo da circulação fetal: revisão do aspecto segurança

Os autores apresentam os métodos Doppler e sua evolução no estudo da circulação fetal, dando ênfase à segurança e aos bioefeitos. Os aparelhos de ultra-sonografia utilizados correntemente funcionam com índice térmico máximo e índice mecânico automaticamente mantidos em níveis inferiores a 1,0. Até os dias atuais, não foi descrita lesão biológica em fetos humanos submetidos ao Doppler diagnóstico. Portanto, o Doppler pulsado, o colorido e o "power" Doppler são seguros na exposição ultra-sonográfica do pré-natal.

Fetal laser therapy: applications in the management of fetal pathologies.

Fetoscopic coagulation of placental anastomoses is the treatment of choice for severe twin-to-twin transfusion syndrome. In the present day, fetal laser therapy is also used to treat amniotic bands, chorioangiomas, sacrococcygeal teratomas, lower urinary tract obstructions and chest masses, all of which will be reviewed in this article. Amniotic band syndrome can cause limb amputation by impairing downstream blood flow. Large chorioangiomas (>4 cm), sacrococcygeal teratomas or fetal hyperechoic lung lesions can lead to fetal compromise and hydrops by vascular steal phenomenon or compression. Renal damage, bladder dysfunction and lastly death because of pulmonary hypolasia may be the result of megacystis caused by a posterior urethral valve. The prognosis of these pathologies can be dismal, and therapy options are limited, which has brought fetal laser therapy to the forefront. Management options discussed here are laser release of amniotic bands, laser coagulation of the placental or fetal tumor feeding vessels and laser therapy by fetal cystoscopy. This review, largely based on case reports, does not intend to provide a level of evidence supporting laser therapy over other treatment options. Centralized evaluation by specialists using strict selection criteria and long-term follow-up of these rare cases are now needed to prove the value of endoscopic or ultrasound-guided laser therapy.

Fetal programming and epigenetic mechanisms in arterial hypertension.

PURPOSE OF REVIEW: To provide an overview of available evidence of the potential role of epigenetics in the pathogenesis of hypertension and vascular dysfunction. RECENT FINDINGS: Arterial hypertension is a highly heritable condition. Surprisingly, however, genetic variants only explain a tiny fraction of the phenotypic variation and the term 'missing heritability' has been coined to describe this phenomenon. Recent evidence suggests that phenotypic alteration that is unrelated to changes in DNA sequence (thereby escaping detection by classic genetic methodology) offers a potential explanation. Here, we present some basic information on epigenetics and review recent work consistent with the hypothesis of epigenetically induced arterial hypertension. SUMMARY: New technologies that enable the rigorous assessment of epigenetic changes and their phenotypic consequences may provide the basis for explaining the missing heritability of arterial hypertension and offer new possibilities for treatment and/or prevention.

Spatio-temporal image correlation (STIC): nova técnica para avaliação do coração fetal

As malformações cardíacas são as mais freqüentes anomalias congênitas ao nascimento, entretanto, a sua detecção pré-natal pela ultra-sonografia convencional permanece baixa. As ultra-sonografias de terceira e quarta dimensões surgiram no início da década de 90, apresentando grandes aplicações em obstetrícia, principalmente nos casos de diagnósticos duvidosos à ultra-sonografia bidimensional. O spatio-temporal image correlation (STIC) representa grande avanço na área de ultra-som de quarta dimensão; constitui-se em um software acoplado ao aparelho Voluson 730 Expert, que permite a aquisição volumétrica do coração fetal e suas conexões vasculares. As análises volumétricas são realizadas nos modos multiplanar e de renderização, podendo-se também utilizar o Doppler. Apresenta, como grandes vantagens, a aquisição rápida e a possibilidade de análise posterior por especialistas em ecocardiografia fetal. Pode ser aplicada para a pesquisa de quaisquer cardiopatias congênitas, pois permite a aquisição de qualquer plano, diferentemente do ultra-som bidimensional. Sua principal desvantagem está relacionada aos movimentos fetais. A maior difusão do método pode permitir um aumento na detecção de malformações cardíacas, pois possibilita ao ultra-sonografista geral encaminhar, via Internet, os volumes para a análise por especialistas em ecocardiografia fetal.

Aplicações da ultra-sonografia tridimensional na avaliação do cerebelo fetal

Nos últimos anos a ultra-sonografia tridimensional tem-se tornado um método de imagem de grande importância no diagnóstico em obstetrícia. Um de seus benefícios seria a maior sensibilidade, em relação ao ultra-som bidimensional, no diagnóstico de algumas malformações fetais. As potenciais aplicações desse novo método seriam uma maior acurácia na medida do volume de órgãos fetais, a possibilidade de rever volumes na ausência da paciente, a possibilidade de utilizar diferentes planos para avaliar determinada estrutura anatômica e a capacidade de transmissão de volumes para centros de referência. A avaliação ultra-sonográfica do cerebelo fetal é de extrema importância, pois, comprovadamente, alterações no seu desenvolvimento estão correlacionadas com alterações do crescimento fetal e anomalias congênitas. O objetivo desta atualização é demonstrar os métodos VOCAL™ e 3D XI™ na avaliação do cerebelo fetal, seus potenciais benefícios e o que há de mais atual na literatura a respeito deste assunto.

O valor da ultra-sonografia e da ressonância magnética fetal na avaliação das hérnias diafragmáticas

OBJETIVO: Demonstrar a significância dos achados da ressonância magnética e da ultra-sonografia na caracterização pré-natal e avaliação do prognóstico de pacientes com hérnia diafragmática congênita. MATERIAIS E MÉTODOS: Catorze gestantes (idade gestacional média de 28,7 semanas) examinadas com ultra-sonografia e apresentando fetos com suspeita de hérnia diafragmática congênita foram avaliadas por meio da ressonância magnética. Os exames foram realizados em aparelho de 1,5 tesla usando seqüências-padrão. Dois radiologistas avaliaram as imagens e estabeleceram os achados por consenso. RESULTADOS: Doze fetos tinham hérnia diafragmática à esquerda e dois, à direita. O fígado fetal foi localizado no interior do tórax de cinco fetos pela ultra-sonografia (três com hérnia diafragmática esquerda e dois com hérnia diafragmática direita) e de oito pela ressonância magnética (seis com hérnia diafragmática esquerda e dois com hérnia diafragmática direita). Herniação do estômago e alças de intestino delgado foi observada em todos os fetos com hérnia diafragmática esquerda (n = 12), tanto pela ultra-sonografia quanto pela ressonância magnética. Oito fetos sobreviveram após cirurgia (sete com hérnia diafragmática esquerda e um com hérnia diafragmática direita). CONCLUSÃO: A ultra-sonografia e a ressonância magnética são métodos de imagens complementares na avaliação das hérnias diafragmáticas congênitas. A ressonância magnética pode auxiliar a ultra-sonografia na avaliação da posição do fígado, o qual representa importante fator prognóstico.